Moderate-to-High Levels of Pretreatment HIV Drug Resistance in KwaZulu-Natal Province, South Africa

Abstract

There is evidence of increasing levels of pretreatment HIV drug resistance (PDR) in Southern Africa. We used data from two large population-based HIV surveillance studies to estimate prevalence of PDR in KwaZulu-Natal, the province with the highest HIV prevalence in South Africa. Sanger sequencing was performed on samples obtained from a longitudinal HIV surveillance program (study A, 2013-2014) and the HIV Incidence Provincial Surveillance System (study B, 2014-2015). Sequences were included for adult HIV positive participants (age ≥15 years for study A, age 15-49 years for study B) with no documented prior exposure to antiretroviral therapy (ART). Overall and drug class-specific PDR was estimated using the World Health Organization 2009 surveillance drug resistance mutation (SDRM) list, and phylogenetic analysis was performed to establish evidence of drug resistance transmission linkage. A total of 1,845 sequences were analyzed (611 study A; 1,234 study B). An overall PDR prevalence of 9.2% [95% confidence interval (CI) 7.0-11.7] was observed for study A and 11.0% (95% CI 8.9-13.2) for study B. In study B, the prevalence of non-nucleoside reverse-transcriptase inhibitor (NNRTI) PDR exceeded 10% for sequences collected in 2014 (10.2%, 95% CI 7.5-12.9). The most prevalent SDRMs were K103NS (7.5%), M184VI (2.4%), and V106AM (1.4%). There was no evidence of large transmission chains of drug-resistant virus. High level NNRTI PDR (>10%) suggests a need to modify the standard first-line ART regimen and to focus attention on improving the quality of HIV prevention, treatment, and care.

Keywords: HIV; South Africa; antiretroviral therapy; molecular epidemiology; pretreatment drug resistance; surveillance.

FIG. 1.

Location of the two population-based studies.

FIG. 2.

Summary of the specimens and HIV-1 sequences from the two studies in KZN, South Africa. ^aExcluded due to incomplete RT sequences. KZN, KwaZulu-Natal Province; RT, reverse transcriptase.

FIG. 3.

Levels of pretreatment drug resistance (A) and NNRTI-specific pretreatment drug resistance (B). Marker line in (B) corresponds to 10% threshold for NNRTI PDR. Prevalence estimates and confidence intervals for study B were weighted to adjust for the survey design and for nonresponse across age and gender categories. NNRTI, non-nucleoside reverse-transcriptase inhibitor; PDR, pretreatment HIV drug resistance.